Enzymatic Basis of Detoxication Volume 1

Enzymatic Basis of Detoxication, Volume I focuses on the catalytic mechanisms and physiological expression of the enzymes that are involved in the detoxication of foreign compounds. The book explores foreign compound metabolism at the level of what specific enzymes can do. This book is organized into three sections and comprised of 17 chapters. The discussion begins with an overview of detoxication and covers both catalytic and non-catalytic removal of foreign substances, along with the general properties of the enzymes that are active in detoxication. The reader is then introduced to the physiological aspects of detoxication, paying particular attention to the kinetic aspects of metabolism and elimination of foreign compounds in animals, human genetic variation in detoxication enzymes, and how such enzymes are induced. The next section focuses on mixed function oxygenase systems and includes chapters on cytochrome P-450 and the detoxication reactions it catalyzes. The book also considers other oxidation-reduction systems, with reference to alcohol dehydrogenase, aldehyde reductase, aldehyde oxidizing enzymes, ketone reductases, xanthine oxidase and aldehyde oxidase, glutathione peroxidase, and superoxide dismutases. The final chapter is devoted to monoamine oxidase, its properties, substrate specificity, inhibitors, kinetics and mechanism, and multiple forms. Pharmacologists, toxicologists, and biochemists will find this book extremely helpful.

Table of Contents:
List of ContributorsPrefaceContents of Volume II Chapter 1 Detoxication Enzymes I. Detoxication II. Characterization of the Enzymes of Detoxication III. The Question of Natural Substrate 5 References References Chapter 2 Kinetic Aspects of Metabolism and Elimination of Foreign Compounds in Animals I. Introduction II. Pharmacokinetic Model III. Comments References Chapter 3 Human Genetic Variation in the Enzymes of Detoxication I. Introductory Remarks II. Classification of Human Pharmacogenetic Disorders III. Avenues for Future Exploration IV. Comments References Chapter 4 Induction of the Enzymes of Detoxication I. Introduction II. Induction of Mixed Function Oxidases III. Chromatin Activation IV. Effects on RNA Polymerase V. Effects on Components on Protein Synthesis VI. Comments References Chapter 5 Comparative Aspects of Detoxication in Mammals I. Introduction II. The Origins of Species Differences in Foreign Compound Metabolism III. Do "Species Patterns" of Foreign Compound Metabolism Exist? IV. The Significance of the Comparative Biochemistry of Foreign Compounds for Animal Taxonomy V. The Enzymatic Basis of Species Differences in Foreign Compound Metabolism VI. Comments References Part II. Mixed Function Oxygenase Systems Chapter 6 Microsomal Cytochrome P-450: A Central Catalyst in Detoxication Reactions I. Introduction II. Purification Procedures III. Enzyme Assays IV. Characterization of Purified Enzymes V. Substrate Specificity VI. Summary and Comments on Factors Controlling Activities of Cytochrome P-450 References Chapter 7 Reactions Catalyzed by the Cytochrome P-450 System I. Introduction II. Criteria Used to Establish the Involvement of Cytochrome P-450 in Various Reactions III. Oxidative Reactions IV. Reductive Reactions V. Comments References Chapter 8 The Role of NADPH-Cytochrome c (P-450) Reductase in Detoxication I. Introduction II. Microsomal Electron Transport Systems III. Purification of NADPH-Cytochrome c (P-450) Reductase IV. Properties of NADPH-Cytochrome c (P-450) Reductase from Various Organs and Species V. Specificity of Reductase-Cytochrome P-450 Interaction in Various Monooxygenase Reactions; Other Metabolic Functions Chapter 9 Microsomal Flavin-Containing Monooxygenase: Oxygenation of Nucleophilic Nitrogen and Sulfur Compounds I. Introduction II. Hog Liver Microsomal Flavin-Containing Monooxygenase III. Species and Tissue Distribution References Part III. Other Oxidation-Reduction Systems Chapter 10 Alcohol Dehydrogenase I. Introduction II. Distribution of Alcohol Dehydrogenase III. Multiple Molecular Forms of Human Liver Alcohol Dehydrogenase IV. Purification of Human Liver Alcohol Dehydrogenase V. Molecular Properties of Human Liver Alcohol Dehydrogenase VI. Catalytic Properties of Human Liver Alcohol Dehydrogenase VII. Regulation of Ethanol Metabolism in Man References Chapter 11 Aldehyde Reductase I. Introduction II. Distribution of Aldehyde Reductases III. Purification and Assay IV. Structural Properties V. Catalytic Properties References Chapter 12 Aldehyde Oxidizing Enzymes I. Introduction II. Aldehyde Dehydrogenases III. Nonspecific Aldehyde Dehydrogenase IV. Formaldehyde Dehydrogenase V. Aldehyde Oxidase VI. Comments References Chapter 13 Ketone Reductases I. Introduction II. Assay III. Purification IV. Distribution V. Specificity and Characterization VI. Comments References Chapter 14 Xanthine Oxidase and Aldehyde Oxidase I. Introduction II. Electron Donor Specificity III. Electron Acceptor Specificity IV. Inhibitors V. Human Enzymes VI. Relevance to Detoxication VII. Purification and Assay VIII. Regulation IX. Comments References Chapter 15 Superoxide Dismutases: Detoxication of a Free Radical I. Introduction II. Intermediates of Oxygen Reduction III. O2- as Substrate IV. Superoxide Dismutase—The Enzyme V. The Physiological Role of Superoxide Dismutases References Chapter 16 Glutathione Peroxidase I. Introduction II. The Role of Glutathione Peroxidase in Hydroperoxide Metabolism III. Determination of Glutathione Peroxidase Activity and Definition of Units IV. Purification V. Physical and Chemical Properties VI. Kinetic Data VII. Active Site, Structure, and Mechanism of Catalysis VIII. Distribution of Glutathione Peroxidase IX. Comments References Chapter 17 Monoamine Oxidase I. Introduction II. Assay and Purification III. Substrate Specificity IV. Properties of the Enzyme V. Inhibitors VI. Kinetics and Mechanism VII. Multiple Forms References